Bombesin and its mammalian counterpart, gastrin releasing peptide, are members of the group of ubiquitous neurogastrointestinal peptides and are distributed throughout the CNS, lungs, and GI tract. Principal biological activities include potent stimulation of gastrin release, probably by direct action on gastrin-producing cells, stimulation of pancreatic enzyme release, and stimulation of pituitary GH release. Recently it has been shown that human lung oat cell carcinomas secrete and contain large amounts of bombesin-like peptide and it has been suggested that bombesin could be a growth factor for these tumors and also responsible for many of the side-effects created by the disease. We propose to carry out structure-activity studies on synthetic analogs of the C-terminal octapeptide region of bombesin which appears to be the shortest fragment to retain full biological activity. The primary aim of this project would be to develop potent competitive antagonists of the peptide. Not only would such compounds be of enormous value in elucidating the many physiological roles and mechanisms of action of bombesin, but could also be of potential therapeutic use in the control of growth of certain lung cancers and the side-effects associated with hypersecretion of bombesin. It is also possible that an antagonist would offer a novel route for control of gastric acid secretion which also has some therapeutic implications. Bombesin analogs will be synthesized by automated solid-phase methods, purified by preparative HPLC, and assayed in vitro for effects on release of amylase from dispersed rat acinar cells and in vivo for effects on immunoreactive gastrin release also in the rat. Studies of the effects of bombesin and its antagonists on the release of several other peptide hormones are also contemplated.